4910
A. F. C. Flores et al. / Tetrahedron Letters 51 (2010) 4908–4910
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. Fax +44 0 1223
336033, email: deposit@ccdc.cam.ac.uk.
15. Snider, B. B.; Neubert, B. J. J. Org. Chem. 2004, 69, 8953–8955.
synthesis of functionalized 5-propylidene-1H-pyrrolidin-2-one
derivatives was obtained in several reaction steps, or using expen-
sive reagents.6–12,15
All common reagents and solvents were used as obtained from
commercial suppliers without further purification. All melting points
were determined on a Reichert Thermovar apparatus and are uncor-
rected. 1H and 13C NMR spectra were acquired on a Bruker DPX
400spectrometer (1H at 400.13 MHz and 13C at 100.63 MHz), 5 mm
sample tubes, 298 K, digital resolution 0.01 ppm, in CDCl3, and
TMS as internal reference.
The general procedure for 1-alkyl(aryl)-4-bromo-5-(3,3,3-tri-
halo-2-oxopropylidene)-1H-pyrrolidin-2-ones (3a–d, 4a–d) with
molecular bromine: to a stirred solution of 1-alkyl(aryl)-5-(3,3,3-tri-
halo-2-oxopropylidene)-1H-pyrroli din-2-one (2 mmol) in methy-
lene chloride (5 mL) was added dropwise a solution of molecular
bromine in methylene chloride. The mixture was stirred for 4 h at
room temperature. Then the mixture was cooled in ice bath, at
À4 °C, and to which was added a solution with pyridine (2 mmol)
in methylene chloride. The resulting solution was stirred for
30 min. Then, it was washed with water (3 Â 15 mL), and the organ-
ic layer was dried over Na2SO4. The solvent was evaporated to give
pure products 3a–d and 4a–d. Products were fully characterized by
elemental analysis and NMR data.16
16. For 3a: 86%, red-brown oil, 1H NMR d 5.85 (s, 1H, H-6), 5.78 (d, 1H, JHH = 7 Hz,
H-4), 3.75 (m, 1H, H-9), 3.52 (m, 1H, H-9), 3.26 (dd, 1H, JHH = 19 and 7 Hz, H-3),
3.03 (d, 1H, JHH = 19 Hz, H-3), 1.69 (sx, 2H, JHH = 7 Hz, H-10), 0.99 (t, 3H,
JHH = 7 Hz, H-11). 13C NMR d 177.7 (q, JCF = 35 Hz, C-7), 173 (C-5), 165.6 (C-2),
116.1 (q, JCF = 291 Hz, C-8), 91.5 (C-6), 42.4 (C-9), 39.7 (C-3), 36 (C-4), 19.4 (C-10),
11 (C-11). MS m/z (%) 315(M++2, 10), 313 (M+, 8), 244 (39), 234 (100), 204 (15),
108 (35). Compound 3b: 91%, red oil, 1H NMR d 7.38–7.23 (m, 5H, Ph), 5.81 (s, 1H,
H-6), 5.75 (d, 1H, JHH = 7 Hz, H-4), 4.95 (d, 1H, JHH = 16 Hz, H-9), 4.71 (d, 1H,
JHH = 16 Hz, H-9), 3.32 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.09 (d, 1H, JHH = 19 Hz,
H-3). 13C NMR d 177.6 (q, JCF = 35 Hz, C-7), 172.9 (C-5), 164.7 (C-2), 133, 129, 128.3,
127 (Ph), 115.9 (q, JCF = 291 Hz, C-8), 92.8 (C-6), 44.4 (C-9), 39.7 (C-3), 35.9 (C-4).
MS m/z (%) 364(M++2, <5), 362 (M+, <5), 292 (9), 282 (100), 204 (15), 91 (67).
Compound 3c: 90%, white solid, mp 77–79 °C, 1H NMR d 7.61–7.24 (m, 5H, Ph),
5.89 (d, 1H, JHH = 7 Hz, H-4), 5.66 (d, 1H, H-6), 3.44 (dd, 1H, JHH = 19 and 7 Hz, H-
3), 3.16 (d, 1H, JHH = 19 Hz, H-3). 13C NMR d 178.2 (q, JCF = 35 Hz, C-7), 172.3 (C-5),
166.4 (C-2), 132.4, 130.2, 130, 126.9 (Ph), 115.9 (q, JCF = 291 Hz, C-8), 93.3 (C-6),
40.1 (C-3), 36.2 (C-3). MS m/z (%) 349(M++2, <5), 347 (M+, <5), 278 (9), 268 (16),
198 (75), 170 (38), 144 (22), 77 (100). Compound 3d: 80%, yellow solid, mp 139–
141 °C, 1H NMR d 7.72 (m, 2H, Ar), 7.15 (m, 2H, Ar), 5.89 (d, 1H, JHH = 7 Hz, H-4),
5.67 (d, 1H, H-6), 3.43 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.17 (d, 1H, JHH = 19 Hz, H-
3). 13C NMR d 178 (q, JCF = 35 Hz, C-7), 172 (C-5), 165.9 (C-2), 133.5, 131.3, 128.5,
120.1 (Ar), 115.8 (q, JCF = 291 Hz, C-8), 93.2 (C-6), 40 (C-4), 36.1 (C-3). Compound
4a: 79%, brown oil, 1H NMR d 6.15 (s, 1H, H-6), 5.83 (d, 1H, JHH = 7 Hz, H-4), 3.78
(m, 1H, H-9), 3.53 (m, 1H, H-9), 3.26 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.03 (d, 1H,
JHH = 19 Hz, H-3), 1.70 (sx, 2H, JHH = 7 Hz, H-10), 0.99 (t, 3H, JHH = 7 Hz, H-11). 13
C
NMR d 178.7 (C-7), 172.8 (C-5), 164.3 (C-2), 96.9 (C-8), 91.4 (C-6), 42.3 (C-9), 39.9
(C-3), 35.9 (C-4), 19.5 (C-10), 11.1 (C-11). MS m/z (%) 364(M++2, <5), 362 (M+, <5),
246 (100), 244 (90), 204 (13), 202 (10), 164 (55), 122 (58), 80 (20), 78 (18).
Compound 4b: 97%, brown oil, 1H NMR d 7.37–7.25 (m, 5H, Ph), 6.11 (s, 1H, H-6),
5.79 (d, 1H, JHH = 7 Hz, H-4), 4.98 (d, 1H, JHH = 16 Hz, H-9), 4.74 (d, 1H,
JHH = 16 Hz, H-9), 3.33 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.11 (d, 1H, JHH = 19 Hz,
H-3). 13C NMR d 178.5 (C-7), 172.8 (C-5), 163.1 (C-2), 133.3, 129, 128.3, 127.3
(Ph), 96.7 (C-8), 93.1 (C-6), 44.5 (C-9), 40 (C-3), 35.7 (C-4). Compound 4c: 89%,
yellow solid, mp 118–120 °C, 1H NMR d 7.60–7.27 (m, 5H, Ph), 5.99 (d, 1H, H-6),
5.95 (d, 1H, JHH = 7 Hz, H-4), 3.47 (dd, 1H, JHH = 19 and 7 Hz, H-3), 3.17 (d, 1H,
JHH = 19 Hz, H-3). 13C NMR d 179 (C-7), 172.1 (C-5), 165.2 (C-2), 132.7, 130.1,
129.8, 126.9 (Ph), 96.6 (q, JCF = 291 Hz, C-8), 93.3 (C-6), 40.4 (C-3), 36.2 (C-4).
Compound 4d: 91%, yellow solid, mp 146–148 °C, 1H NMR d 7.75 (m, 2H, Ar), 7.14
(m, 2H, Ar), 5.99 (d, 1H, H-6), 5.94 (d, 1H, JHH = 7 Hz, H-4), 3.46 (dd, 1H, JHH = 19
and 7 Hz, H-3), 3.17 (d, 1H, JHH = 19 Hz, H-3). 13C NMR d 178.9 (q, JCF = 35 Hz, C-7),
171.8 (C-5), 164.5 (C-2), 133.4, 131.7, 128.5, 123.9 (Ar), 96.5 (C-8), 93.4 (C-6),
40.3 (C-4), 36 (C-3).
The general procedure for 1-alkyl(aryl)-5-(3,3,3-trihalo-2-oxo-
propylidene)-1H-pyrrol-2(5H)-ones (5a–d, 6a–d): to
a stirred
solution of 1-alkyl(aryl)-4-bromo-5-(3,3,3-trihalo-2-oxopropylid-
ene)-1H-pyrrolidin-2-one (2 mmol) in methylene chloride (5 mL)
at 0 °C was dropwise added a solution of triethylamine (2.1 mmol)
in methylene chloride (5 mL). The mixture was stirred for 15 min.
Then the mixture was washed with water (3 Â 15 mL), and the
organic layer was dried over MgSO4. The solvent was evaporated
to give pure products 5a–d and 6a–d. Products were fully charac-
terized by elemental analysis and NMR data.17
17. For 5a: 92%, yellow oil, 1H NMR d 8.06 (d, 1H, JHH = 6 Hz, H-3), 6.38 (dd, 1H,
Acknowledgments
4
3
3JHH = 6 Hz, JHH = 1 Hz, H-4), 5.94 (s, 1H, H-6), 3.53 (t, 2H, JHH = 7 Hz, H-9),
1.56 (sx, 2H, JHH = 7 Hz, H-10), 0.87 (t, 3H, JHH = 7 Hz, H-11). 13C NMR d 179.2
3
The authors thank the Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq- Process No. 306938/2007-3 and
No 476158/2007-9) for the financial support and PIBIC-fellowship
(for J. L. Malavolta). The financial support from Fundação de Apoio
a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) is also
acknowledged.
(q, JCF = 35 Hz, C-7), 170.2 (C-2), 156.1 (C-5), 136.4 (C-3), 128.7 (C-4), 116.0 (q,
JCF = 291 Hz, C-8), 95.7 (C-6), 41.2 (C-9), 21.5 (C-10), 11.2 (C-11). MS m/z (%)
233 (M+, 32), 164 (100), 136 (30). Compound 5b: 87%, yellow oil, 1H NMR d
3
3
8.13 (d, 1H, JHH = 6 Hz, H-3), 7.37–7.18 (m, 5H, Ph), 6.52 (dd, 1H, JHH = 6 Hz,
4JHH = 1 Hz, H-4), 5.99 (s, 1H, H-6), 4.83 (s, 2H, H-9). 13C NMR d 179.1 (q,
JCF = 35 Hz, C-7), 170 (C-2), 155.4 (C-5), 136.7 (C-3), 134.9, 129, 128.7, 128.1,
127 (Ph), 115.8 (q, JCF = 291 Hz, C-8), 96.9 (C-6), 43.2 (C-9). MS m/z (%) 281(M+,
100), 212 (13), 184 (30), 91 (69). Compound 5c: 94%, white solid, mp 98–99 °C,
3
1H NMR d 8.28 (d, 1H, JHH = 6 Hz, H-3), 7.6–7.21 (m, 5H, Ph), 6.58 (dd, 1H,
3JHH = 6 Hz, 4JHH = 1 Hz, H-4), 5.95 (s, 1H, H-6). 13C NMR d 179.4 (q, JCF = 36 Hz,
C-7), 169.3 (C-2), 156.5 (C-5), 136.5 (C-3), 132.2, 129.9, 129.3, 128.6, 123.4
(Ph), 115.8 (q, JCF = 291 Hz, C-8), 97.3 (C-6). MS m/z (%) 267 (M+, 39), 198 (100),
170 (51), 144 (9), 77 (28). Compound 5d: 94%, yellow oil. 1H NMR d 8.28 (d, 1H,
Supplementary data
Supplementary data associated with this article can be found, in
3
3JHH = 6 Hz, H-3), 7.71 (m, 2H, Ar), 7.12 (m, 2H, Ar), 6.58 (dd, 1H, JHH = 6 Hz,
4JHH = 1 Hz, H-4), 5.94 (d, 1H, H-6). 13C NMR d 179.4 (q, JCF = 36 Hz, C-7), 169 (C-
2), 156 (C-5), 136.7 (C-3), 133.2, 131.2, 129.4 (Ar), 128.6 (C-4), 123.4 (Ar), 115.7
(q, JCF = 291 Hz, C-8), 97.4 (C-6). MS m/z (%) 347 (M++2, 25), 345 (M+, 25), 276
(58), 248 (9), 169 (100). Compound 6a: 89%, white solid, mp 52–53 °C. 1H NMR
d 8.18 (d, 1H, 3JHH = 6 Hz, H-3), 6.43 (dd, 1H, 3JHH = 6 Hz, 4JHH = 1 Hz, H-4), 6.37
References and notes
1. Flores, A. F. C.; Flores, D. C.; Oliveira, G.; Pizzuti, L.; Silva, R. M. S.; Martins, M. A.
P.; Bonacorso, H. G. J. Braz. Chem. Soc. 2008, 19, 184–193.
2. Piovesan, L. A. Ph.D. Dissertation, Federal University of Santa Maria, 2009.
3. Martins, M. A. P.; Sinhorin, A. P.; Rosa, A.; Flores, A. F. C.; Wastowski, A. D.;
Pereira, C. M. P.; Flores, D. C.; Beck, P.; Freitag, R. A.; Brondani, S.; Cunico, W.;
Bonacorso, H. G.; Zanatta, N. Synthesis 2002, 2353–2357.
4. Tsolomiti, G.; Tsolomitis, A. Tetrahedron Lett. 2004, 45, 9353–9355.
5. Pinheiro, S.; da Silva, R. C., Jr.; Souza, A. S.; Carneiro, J. W.; Muri, E. M. F.;
Antunes, O. A. C. Tetrahedron Lett. 2009, 50, 2402–2404.
4
3
3
(d, 1H, JHH = 1 Hz, H-6), 3.64 (t, 2H, JHH = 7 Hz, H-9), 1.65 (sx, 2H, JHH = 7 Hz,
H-10), 0.95 (t, 3H, JHH = 7 Hz, H-11). 13C NMR d 179.4 (C-7), 170 (C-2), 155.3 (C-
5), 135.9 (C-3), 128.2 (C-4), 96.7 (C-6), 96 (C-8), 41 (C-9), 21.6 (C-10), 11.2 (C-
11). MS m/z (%) 281 (M+, <5), 164 (100), 145 (14), 122 (31). Compound 6b: 93%,
white solid, mp 92–94 °C. 1H NMR d 8.17 (d, 1H, JHH = 6 Hz, H-3), 7.38–7.20
3
(m, 5H, Ph), 6.5 (dd, 1H, 3JHH = 6 Hz, 4JHH = 1 Hz, H-4), 6.33 (s, 1H, H-6), 4.86 (s,
2H, H-9). 13C NMR d 179.3 (C-7), 169.9 (C-2), 154.5 (C-5), 136.2 (C-3), 135.3,
128.9, 128.1, 128, 127.2 (Ph), 97.6 (C-6), 96.5 (C-8), 43.3 (C-9). MS m/z (%) 331
(M++2, 12), 329 (M+, 13), 294 (46), 212 (59), 184 (5), 91 (100). Compound 6c:
88%, white solid, mp 130–132 °C, 1H NMR d 8.33 (d, 1H, 3JHH = 6 Hz, H-3), 7.56–
6. Taylor, J. M.; Abell, A. D. J. Org. Chem. 1993, 58, 14–15.
7. Abell, A. D.; Oldham, M. D.; Taylor, J. M. J. Org. Chem. 1995, 60, 1214–1220.
8. Langer, P.; Döring, M. Synlett 2001, 1437–1439.
3
4
7.26 (m, 5H, Ph), 6.56 (dd, 1H, JHH = 6 Hz, JHH = 1 Hz, H-4), 6.31 (d, 1H,
4JHH = 1 Hz, H-6). 13C NMR d 179.7 (C-7), 169.3 (C-2), 155.8 (C-5), 136.1 (C-3),
132.5, 129.8 (Ph), 129 (C-4), 128.1, 127.7 (Ph), 97.9 (C-6), 96.4 (C-8). MS m/z (%)
317 (M++2, <5), 315 (M+, <5), 198 (100), 170 (23), 144 (9), 77 (28). Compound
6d: 86%, yellow solid, mp 127–130 °C, 1H NMR d 8.33 (d, 1H, 3JHH = 6 Hz, H-3),
7.69 (m, 2H, Ar), 7.15 (m, 2H, Ar), 6.56 (dd, 1H, JHH = 6 Hz, JHH = 1 Hz, H-4),
6.31 (d, 1H, H-6). 13C NMR d 179.6 (C-7), 169 (C-2), 155.2 (C-5), 136.3 (C-3),
133.1, 131.5, 129.3 (Ar), 128.1 (C-4), 123.1 (Ar), 98 (C-8), 96.3 (C-6). MS m/z (%)
395 (M++2, <5), 393 (M+, <5), 276 (100), 248 (8), 169 (30).
9. Singh, V.; Saxena, R.; Batra, S. J. Org. Chem. 2005, 70, 353–356.
10. Blaszczyk, E.; Krawczyk, H.; Janecki, T. Synlett 2004, 2685–2688.
11. Nagasaka, T.; Koseki, Y.; Kusano, S. Tetrahedron Lett. 1998, 39, 3517–3520.
12. Dieter, R. K.; Lu, K. Tetrahedron Lett. 1999, 40, 4011–4014.
13. Pizzuti, L. Ph.D. Dissertation, Federal University of Santa Maria, 2008.
14. Crystallographic data for compound 3d have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication
number 740176. Copies of the data can be obtained free of charge, on
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4